sharon sanders
Editor-in-Chief & President
Original Investigation
September 30, 2020
Efficacy and Safety of Hydroxychloroquine vs Placebo for Pre-exposure SARS-CoV-2 Prophylaxis Among Health Care Workers
A Randomized Clinical Trial
Benjamin S. Abella, MD, MPhil[SUP]1[/SUP]; Eliana L. Jolkovsky, BA[SUP]1[/SUP]; Barbara T. Biney, MPH[SUP]1[/SUP]; et alJulie E. Uspal, MD[SUP]1[/SUP]; Matthew C. Hyman, MD, PhD[SUP]2[/SUP]; Ian Frank, MD[SUP]3[/SUP]; Scott E. Hensley, PhD[SUP]4[/SUP]; Saar Gill, MD, PhD[SUP]5[/SUP]; Dan T. Vogl, MD, MSCE[SUP]5[/SUP]; Ivan Maillard, MD, PhD[SUP]5[/SUP]; Daria V. Babushok, MD[SUP]5[/SUP]; Alexander C. Huang, MD, PhD[SUP]5[/SUP]; Sunita D. Nasta, MD[SUP]5[/SUP]; Jennifer C. Walsh[SUP]5[/SUP]; E. Paul Wiletyo, PhD[SUP]6[/SUP]; Phyllis A. Gimotty, PhD[SUP]6[/SUP]; Michael C. Milone, MD, PhD[SUP]7[/SUP]; Ravi K. Amaravadi, MD[SUP]5[/SUP];
Author Affiliations Article Information
JAMA Intern Med. Published online September 30, 2020. doi:10.1001/jamainternmed.2020.6319
Key Points
Question Does a regimen of hydroxychloroquine, 600 mg, per day, reduce the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as a pre-exposure prophylaxis strategy when taken by hospital-based health care workers?
Finding In this double-blind, placebo-controlled randomized clinical trial that included 132 participants and was terminated early, there was not a significant difference in reverse-transcriptase polymerase chain reaction–confirmed SARS-CoV-2 incidence between hydroxychloroquine and placebo cohorts.
Meaning Among hospital-based health care workers, daily hydroxychloroquine did not prevent SARS-CoV-2 infection, although the trial was terminated early and may have been underpowered to detect a clinically important difference.
Abstract
Importance Health care workers (HCWs) caring for patients with coronavirus disease 2019 (COVID-19) are at risk of exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Currently, to our knowledge, there is no effective pharmacologic prophylaxis for individuals at risk.
Objective To evaluate the efficacy of hydroxychloroquine to prevent transmission of SARS-CoV-2 in hospital-based HCWs with exposure to patients with COVID-19 using a pre-exposure prophylaxis strategy.
Design, Setting, and Participants This randomized, double-blind, placebo-controlled clinical trial (the Prevention and Treatment of COVID-19 With Hydroxychloroquine Study) was conducted at 2 tertiary urban hospitals, with enrollment from April 9, 2020, to July 14, 2020; follow-up ended August 4, 2020. The trial randomized 132 full-time, hospital-based HCWs (physicians, nurses, certified nursing assistants, emergency technicians, and respiratory therapists), of whom 125 were initially asymptomatic and had negative results for SARS-CoV-2 by nasopharyngeal swab. The trial was terminated early for futility before reaching a planned enrollment of 200 participants.
Interventions Hydroxychloroquine, 600 mg, daily, or size-matched placebo taken orally for 8 weeks.
Main Outcomes and Measures The primary outcome was the incidence of SARS-CoV-2 infection as determined by a nasopharyngeal swab during the 8 weeks of treatment. Secondary outcomes included adverse effects, treatment discontinuation, presence of SARS-CoV-2 antibodies, frequency of QTc prolongation, and clinical outcomes for SARS-CoV-2–positive participants.
Results Of the 132 randomized participants (median age, 33 years [range, 20-66 years]; 91 women [69%]), 125 (94.7%) were evaluable for the primary outcome. There was no significant difference in infection rates in participants randomized to receive hydroxychloroquine compared with placebo (4 of 64 [6.3%] vs 4 of 61 [6.6%]; P > .99). Mild adverse events were more common in participants taking hydroxychloroquine compared with placebo (45% vs 26%; P = .04); rates of treatment discontinuation were similar in both arms (19% vs 16%; P = .81). The median change in QTc (baseline to 4-week evaluation) did not differ between arms (hydroxychloroquine: 4 milliseconds; 95% CI, −9 to 17; vs placebo: 3 milliseconds; 95% CI, −5 to 11; P = .98). Of the 8 participants with positive results for SARS-CoV-2 (6.4%), 6 developed viral symptoms; none required hospitalization, and all clinically recovered.
Conclusions and Relevance In this randomized clinical trial, although limited by early termination, there was no clinical benefit of hydroxychloroquine administered daily for 8 weeks as pre-exposure prophylaxis in hospital-based HCWs exposed to patients with COVID-19.
Trial Registration ClinicalTrials.gov Identifier: NCT04329923
https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2771265
September 30, 2020
Efficacy and Safety of Hydroxychloroquine vs Placebo for Pre-exposure SARS-CoV-2 Prophylaxis Among Health Care Workers
A Randomized Clinical Trial
Benjamin S. Abella, MD, MPhil[SUP]1[/SUP]; Eliana L. Jolkovsky, BA[SUP]1[/SUP]; Barbara T. Biney, MPH[SUP]1[/SUP]; et alJulie E. Uspal, MD[SUP]1[/SUP]; Matthew C. Hyman, MD, PhD[SUP]2[/SUP]; Ian Frank, MD[SUP]3[/SUP]; Scott E. Hensley, PhD[SUP]4[/SUP]; Saar Gill, MD, PhD[SUP]5[/SUP]; Dan T. Vogl, MD, MSCE[SUP]5[/SUP]; Ivan Maillard, MD, PhD[SUP]5[/SUP]; Daria V. Babushok, MD[SUP]5[/SUP]; Alexander C. Huang, MD, PhD[SUP]5[/SUP]; Sunita D. Nasta, MD[SUP]5[/SUP]; Jennifer C. Walsh[SUP]5[/SUP]; E. Paul Wiletyo, PhD[SUP]6[/SUP]; Phyllis A. Gimotty, PhD[SUP]6[/SUP]; Michael C. Milone, MD, PhD[SUP]7[/SUP]; Ravi K. Amaravadi, MD[SUP]5[/SUP];
Author Affiliations Article Information
JAMA Intern Med. Published online September 30, 2020. doi:10.1001/jamainternmed.2020.6319
Key Points
Question Does a regimen of hydroxychloroquine, 600 mg, per day, reduce the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as a pre-exposure prophylaxis strategy when taken by hospital-based health care workers?
Finding In this double-blind, placebo-controlled randomized clinical trial that included 132 participants and was terminated early, there was not a significant difference in reverse-transcriptase polymerase chain reaction–confirmed SARS-CoV-2 incidence between hydroxychloroquine and placebo cohorts.
Meaning Among hospital-based health care workers, daily hydroxychloroquine did not prevent SARS-CoV-2 infection, although the trial was terminated early and may have been underpowered to detect a clinically important difference.
Abstract
Importance Health care workers (HCWs) caring for patients with coronavirus disease 2019 (COVID-19) are at risk of exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Currently, to our knowledge, there is no effective pharmacologic prophylaxis for individuals at risk.
Objective To evaluate the efficacy of hydroxychloroquine to prevent transmission of SARS-CoV-2 in hospital-based HCWs with exposure to patients with COVID-19 using a pre-exposure prophylaxis strategy.
Design, Setting, and Participants This randomized, double-blind, placebo-controlled clinical trial (the Prevention and Treatment of COVID-19 With Hydroxychloroquine Study) was conducted at 2 tertiary urban hospitals, with enrollment from April 9, 2020, to July 14, 2020; follow-up ended August 4, 2020. The trial randomized 132 full-time, hospital-based HCWs (physicians, nurses, certified nursing assistants, emergency technicians, and respiratory therapists), of whom 125 were initially asymptomatic and had negative results for SARS-CoV-2 by nasopharyngeal swab. The trial was terminated early for futility before reaching a planned enrollment of 200 participants.
Interventions Hydroxychloroquine, 600 mg, daily, or size-matched placebo taken orally for 8 weeks.
Main Outcomes and Measures The primary outcome was the incidence of SARS-CoV-2 infection as determined by a nasopharyngeal swab during the 8 weeks of treatment. Secondary outcomes included adverse effects, treatment discontinuation, presence of SARS-CoV-2 antibodies, frequency of QTc prolongation, and clinical outcomes for SARS-CoV-2–positive participants.
Results Of the 132 randomized participants (median age, 33 years [range, 20-66 years]; 91 women [69%]), 125 (94.7%) were evaluable for the primary outcome. There was no significant difference in infection rates in participants randomized to receive hydroxychloroquine compared with placebo (4 of 64 [6.3%] vs 4 of 61 [6.6%]; P > .99). Mild adverse events were more common in participants taking hydroxychloroquine compared with placebo (45% vs 26%; P = .04); rates of treatment discontinuation were similar in both arms (19% vs 16%; P = .81). The median change in QTc (baseline to 4-week evaluation) did not differ between arms (hydroxychloroquine: 4 milliseconds; 95% CI, −9 to 17; vs placebo: 3 milliseconds; 95% CI, −5 to 11; P = .98). Of the 8 participants with positive results for SARS-CoV-2 (6.4%), 6 developed viral symptoms; none required hospitalization, and all clinically recovered.
Conclusions and Relevance In this randomized clinical trial, although limited by early termination, there was no clinical benefit of hydroxychloroquine administered daily for 8 weeks as pre-exposure prophylaxis in hospital-based HCWs exposed to patients with COVID-19.
Trial Registration ClinicalTrials.gov Identifier: NCT04329923
https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2771265
